The long?term objective of the proposed research is to understand the role of genome topological domains as Project Summary the functional and structural units in genome. It also aims to discover the localization preferences of Xist transcripts on chromosome X. Specifically, the proposed research will: 1. Discover the topological and epigenetic preferences of Xist localization on chromosome X by integrating and analyzing the data of multiple histone modifications (ChIP-Seq), CTCF binding (ChIP- Seq), CTCF-CTCF binding (CHIA-PET), Xist localization (RAP), genome topology (Hi-C), and transcribed genes (GRO-seq). 2. Analyze the protein function enrichment of topological domains and regions of chromosome X with various degrees of Xist localization. 3. Implement an ensemble of deep networks to detect boundary of topological domains and predict Xist localization degrees considering two-dimensional or three-dimensional genome topological features and epigenetic properties. 4. Construct the three-dimensional structure of genome topological domains based on normalized Hi-C contacts using an optimization algorithm. 5. Define a novel scoring function to measure both structural signatures and structure-based epigenetic properties of genome topological domain. 6. Cluster topological domains into families based on their structural and epigenetic signatures. 7. Build an online database that interactively visualizes the three-dimensional structure of genome topological domains and dynamically integrates genetic and epigenetic knowledge of the protein-coding genes and non-coding RNA loci existent in each topological domain.